High-Dose Dexamethasone and Oxygen Support Strategies in Intensive Care Unit Patients With Severe COVID-19 Acute Hypoxemic Respiratory Failure
Authors: Lila Bouadma, Armand Mekontso-Dessap, Charles Burdet, Hamid Merdji, Julien Poissy, Claire Dupuis, Christophe Guitton, Carole Schwebel, Yves Cohen, Cedric Bruel, Mehdi Marzouk, Guillaume Geri, Charles Cerf, Bruno Mégarbane, Pierre Garçon, Eric Kipnis, Benoit Visseaux, Naima Beldjoudi, Sylvie Chevret, Jean-François Timsit, Naima Beldjoudi , Sylvie Chevret , Charles Burdet , Céline Alloux , Fadila Amerali , Béatrice Andriss , Kamyl Baghli , Hélène Brocvielle , Florence Capelle , Ines Chibane , Sarra Dalibey , Nadia Ettalhaoui , Sabrine Lamri , Yohan Maurer , Jean-Marc Mintsa , Alice Oubahim , Marie-Capucine Tellier , Imane Zemihi , Lila Bouadma , Moustafa Abdel-Nabey , Billal Azzouguen , Ghenima Belkessa , Etienne De Montmollin , Veronique Deiler , Claire Dupuis , Aline Fallet , Guillaume Franchineau , Tiphaine Girard , Alexandra Grinea , Pierre Jaquet, Laura Kramer, Fariza Lamara, Lucie Lefevre, Mehdi Marzouk, Juliette Patrier, Simona Presente, Faiza Sayagh, Fabrice Sinnah, Romain Sonneville, Paul-Henri Wicky, Sylia Zmihi, Yves Cohen, Nathalie Barget, Rawan Belmokhtar, Sabrina Brahmi, Naoual Djabra, Nathan Ebstein, Souha Fliss, Amina Gourbdji, William Juguet, Fadhila Messani, Thomas Rambaud, Vanessa Rathouin, mani Rebai, Marthe Rigal, Julien Schmidt, Marie Soulie, Yacine Tandjaoui-Lombiotte, Anaïs Winchenne, Marianne Ziol, Romain Arrestier, François Bagate, Morgan Benais, Ines Bendib, LE Lan, Brice Benelli, Enora Berti, Astrid Bertier, Guillaume Carteaux, Muriel Carvalho, Pedro Cavaleiro, Nicolas Deprost, Otto Hartman, Anne-Fleur Haudebourg, Delphine Le Febvre De Nailly, Julien Lopinto, Sabrina Mahiou, Paul Masi, Gaël Michaud, Luiza Nait-Chabane, Fariza Ouali, François Perier, Keyvan Razazi, Thiziri Sadaoui, Alaki Thiemele, Samuel Tuffet, Flavien Autron, Pauline Boddaert, Sylvie Brice, Morgan Caplan, Amélie Cerf, Nicolas Cousin, Marie Cuvelliez, Claire Delcourte, Arthur Durand, Raphaël Favory, Ahmed El Kalioubie, Myrtille Gaudel, Alexandre Gaudet, Julien Goutay, Marion Houard , Emmanuelle Jaillette, Mercé Jourdain, Geoffrey Ledoux, Laure Mariller, Guillaume Millot, Anne-Sophie Moreau, Christopher Niles, Saad Nseir, Thierry Onimus , Sébastien Preau, Aurélie Roucou, Anahita Rouze, Ouriel Saura , Arthur Simonnet, Romain Tortuyaux, Hamid Merdji, Hayat Allam, Jessy Cattelan, Raphaël Clere-Jehl, Julie Helms, Kévin Hilt, Anne Hutt-Clauss, Christine Kummerlen, Ferhat Meziani, Alexandra Monnier, Hassène Rahmani, Antoine Studer, Leonie Thiebaut, Aurélie Han Hew Wai, Charles Cerf, David Cortier, Jérôme Devaquet, Dimitri Fremont, Richard Galliot, Fabienne Juster, Mathilde Le Marchand, Lucie Le Meur, Mathilde Neuville, Emmanuel Roux, Guillaume Tachon, Camille Vassord-Dang, Benjamin Zuber, Cédric Bruel, Marie-José Aroulanda, Bryan Berthet-Delteil, Juliette Courtiade-Malher, Alix De Chevigny, Candice Fontaine, Julien Fournier, Sonia Garrigou, Meryam Jardin-Szucs, François Philippart, Sophie Renet, Emmanuelle Sacco, Marc Tran, Christophe Guitton, Delphine Bolle, Jean-Christophe Callahan, Nicolas Chudeau, Cédric Darreau, Séverine Guillarme, Mickael Landais, Laurent Latrouite, Charlène Le Moal, Eliott Lebasnier, Marie-Hélène Leroyer, Rémy Marnai, Juliette Meunier, Catherine Naveau, Marjorie Saint-Martin, Alain Robert, Patrice Tirot, Carole Schwebel, Joanna Bougnaud, Clara Candille, Roselyne Collomb-Muret, Charlotte Cordier, Louis-Marie Galerneau, Côme Gerard, Pierre Nicolas, Amel Refes, Guillaume Rigault, Florian Sigaud, Nicolas Terzi, Ester Terzi, Emmanuelle Turbil, Yann Vallod, Mireille Adda, Claire Bachelier, Marine Bereiziat, Lise Bernard, Radhia Bouzgarrou, Laure Calvet, Pierre Couhault, Elisabeth Coupez, Frédéric Duee, Armelle Gilard, Kévin Grapin, Francis Kinda, Guillaume Laurichesse, Jean-Mathias Liteaudon, Bertrand Souweine, François Thouy, Hervé Declercq, Dominique Descamps, Anne Dewatine, Sabine Janowski, Catherine Senis, Christophe Vinsonneau, Eric Kipnis, Anne Bignon, Tchadie Bommenel, Claude Huriez, Matthieu Duprey, Pierre Garcon, Afef Hammami, Andréa Issad, Marie-Odile Jaccod-Deneuville, Safaâ Kachmar, Ly Van-Vong, Jonathan Zarka, Bruno Megarbane, Nicolas Deye, Aude Jacob, Isabelle Malissin, Aymen M’Rad, Sebastian Voicu, Guillaume Geri, Hélène Chambrin-Lauvray, Ouarda Douache, Mathieu Godement, Romain Jouffroy, Edouard Jullien, Matthieu Petit , Antoine Vieillard-Baron, Alain Cariou, Alexandre Boyer, Patricia Pavese, Bruno Giraudeau
Journal: JAMA Internal Medicine (2022)

The benefit of high-dose dexamethasone and oxygenation strategies vs standard of care for patients with severe acute hypoxemic respiratory failure (AHRF) caused by COVID-19 pneumonia is debated.To assess the benefit of high-dose dexamethasone compared with standard of care dexamethasone, and to assess the benefit of high-flow nasal oxygen (HFNo2) or continuous positive airway pressure (CPAP) compared with oxygen support standard of care (o2SC).This multicenter, placebo-controlled randomized clinical trial was conducted in 19 intensive care units (ICUs) in France from April 2020 to January 2021. Eligible patients were consecutive ICU-admitted adults with COVID-19 AHRF. Randomization used a 2 × 3 factorial design for dexamethasone and oxygenation strategies; patients not eligible for at least 1 oxygenation strategy and/or already receiving invasive mechanical ventilation (IMV) were only randomized for dexamethasone. All patients were followed-up for 60 days. Data were analyzed from May 26 to July 31, 2021.Patients received standard dexamethasone (dexamethasone-phosphate 6 mg/d for 10 days [or placebo prior to RECOVERY trial results communication]) or high-dose dexamethasone (dexamethasone-phosphate 20 mg/d on days 1-5 then 10 mg/d on days 6-10). Those not requiring IMV were additionally randomized to o2SC, CPAP, or HFNo2.The main outcomes were time to all-cause mortality, assessed at day 60, for the dexamethasone interventions, and time to IMV requirement, assessed at day 28, for the oxygenation interventions. Differences between intervention groups were calculated using proportional Cox models and expressed as hazard ratios (HRs).Among 841 screened patients, 546 patients (median [IQR] age, 67.4 [59.3-73.1] years; 414 [75.8%] men) were randomized between standard dexamethasone (276 patients, including 37 patients who received placebo) or high-dose dexamethasone (270 patients). Of these, 333 patients were randomized among o2SC (109 patients, including 56 receiving standard dexamethasone), CPAP (109 patients, including 57 receiving standard dexamethasone), and HFNo2 (115 patients, including 56 receiving standard dexamethasone). There was no difference in 60-day mortality between standard and high-dose dexamethasone groups (HR, 0.96 [95% CI, 0.69-1.33]; P = .79). There was no significant difference for the cumulative incidence of IMV criteria at day 28 among o2 support groups (o2SC vs CPAP: HR, 1.08 [95% CI, 0.71-1.63]; o2SC vs HFNo2: HR, 1.04 [95% CI, 0.69-1.55]) or 60-day mortality (o2SC vs CPAP: HR, 0.97 [95% CI, 0.58-1.61; o2SC vs HFNo2: HR, 0.89 [95% CI, 0.53-1.47]). Interactions between interventions were not significant.In this randomized clinical trial among ICU patients with COVID-19-related AHRF, high-dose dexamethasone did not significantly improve 60-day survival. The oxygenation strategies in patients who were not initially receiving IMV did not significantly modify 28-day risk of IMV requirement.ClinicalTrials.gov Identifier: NCT04344730; EudraCT: 2020-001457-43.